2.50
HDL Handle:
http://hdl.handle.net/10033/239931
Title:
FMNL2 drives actin-based protrusion and migration downstream of Cdc42.
Authors:
Block, Jennifer; Breitsprecher, Dennis; Kühn, Sonja; Winterhoff, Moritz; Kage, Frieda; Geffers, Robert; Duwe, Patrick; Rohn, Jennifer L; Baum, Buzz; Brakebusch, Cord; Geyer, Matthias; Stradal, Theresia E B; Faix, Jan; Rottner, Klemens
Abstract:
Cell migration entails protrusion of lamellipodia, densely packed networks of actin filaments at the cell front. Filaments are generated by nucleation, likely mediated by Arp2/3 complex and its activator Scar/WAVE. It is unclear whether formins contribute to lamellipodial actin filament nucleation or serve as elongators of filaments nucleated by Arp2/3 complex. Here we show that the Diaphanous-related formin FMNL2, also known as FRL3 or FHOD2, accumulates at lamellipodia and filopodia tips. FMNL2 is cotranslationally modified by myristoylation and regulated by interaction with the Rho-guanosine triphosphatase Cdc42. Abolition of myristoylation or Cdc42 binding interferes with proper FMNL2 activation, constituting an essential prerequisite for subcellular targeting. In vitro, C-terminal FMNL2 drives elongation rather than nucleation of actin filaments in the presence of profilin. In addition, filament ends generated by Arp2/3-mediated branching are captured and efficiently elongated by the formin. Consistent with these biochemical properties, RNAi-mediated silencing of FMNL2 expression decreases the rate of lamellipodia protrusion and, accordingly, the efficiency of cell migration. Our data establish that the FMNL subfamily member FMNL2 is a novel elongation factor of actin filaments that constitutes the first Cdc42 effector promoting cell migration and actin polymerization at the tips of lamellipodia.
Affiliation:
Institute of Genetics, University of Bonn, Karlrobert-Kreiten-Strasse 13, 53115 Bonn, Germany.
Citation:
FMNL2 drives actin-based protrusion and migration downstream of Cdc42. 2012, 22 (11):1005-12 Curr. Biol.
Journal:
Current biology : CB
Issue Date:
5-Jun-2012
URI:
http://hdl.handle.net/10033/239931
DOI:
10.1016/j.cub.2012.03.064
PubMed ID:
22608513
Type:
Article
Language:
en
ISSN:
1879-0445
Appears in Collections:
Publikations of the AG Genomanalytik(GMAK)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorBlock, Jenniferen_GB
dc.contributor.authorBreitsprecher, Dennisen_GB
dc.contributor.authorKühn, Sonjaen_GB
dc.contributor.authorWinterhoff, Moritzen_GB
dc.contributor.authorKage, Friedaen_GB
dc.contributor.authorGeffers, Roberten_GB
dc.contributor.authorDuwe, Patricken_GB
dc.contributor.authorRohn, Jennifer Len_GB
dc.contributor.authorBaum, Buzzen_GB
dc.contributor.authorBrakebusch, Corden_GB
dc.contributor.authorGeyer, Matthiasen_GB
dc.contributor.authorStradal, Theresia E Ben_GB
dc.contributor.authorFaix, Janen_GB
dc.contributor.authorRottner, Klemensen_GB
dc.date.accessioned2012-08-24T13:12:54Z-
dc.date.available2012-08-24T13:12:54Z-
dc.date.issued2012-06-05-
dc.identifier.citationFMNL2 drives actin-based protrusion and migration downstream of Cdc42. 2012, 22 (11):1005-12 Curr. Biol.en_GB
dc.identifier.issn1879-0445-
dc.identifier.pmid22608513-
dc.identifier.doi10.1016/j.cub.2012.03.064-
dc.identifier.urihttp://hdl.handle.net/10033/239931-
dc.description.abstractCell migration entails protrusion of lamellipodia, densely packed networks of actin filaments at the cell front. Filaments are generated by nucleation, likely mediated by Arp2/3 complex and its activator Scar/WAVE. It is unclear whether formins contribute to lamellipodial actin filament nucleation or serve as elongators of filaments nucleated by Arp2/3 complex. Here we show that the Diaphanous-related formin FMNL2, also known as FRL3 or FHOD2, accumulates at lamellipodia and filopodia tips. FMNL2 is cotranslationally modified by myristoylation and regulated by interaction with the Rho-guanosine triphosphatase Cdc42. Abolition of myristoylation or Cdc42 binding interferes with proper FMNL2 activation, constituting an essential prerequisite for subcellular targeting. In vitro, C-terminal FMNL2 drives elongation rather than nucleation of actin filaments in the presence of profilin. In addition, filament ends generated by Arp2/3-mediated branching are captured and efficiently elongated by the formin. Consistent with these biochemical properties, RNAi-mediated silencing of FMNL2 expression decreases the rate of lamellipodia protrusion and, accordingly, the efficiency of cell migration. Our data establish that the FMNL subfamily member FMNL2 is a novel elongation factor of actin filaments that constitutes the first Cdc42 effector promoting cell migration and actin polymerization at the tips of lamellipodia.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Current biology : CBen_GB
dc.titleFMNL2 drives actin-based protrusion and migration downstream of Cdc42.en
dc.typeArticleen
dc.contributor.departmentInstitute of Genetics, University of Bonn, Karlrobert-Kreiten-Strasse 13, 53115 Bonn, Germany.en_GB
dc.identifier.journalCurrent biology : CBen_GB

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